** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** AFRICAN SWINE FEVER (ASF) IS AN ACUTE VIRAL DISEASE OF DOMESTIC SWINE WITH MORTALITY RATES APPROACHING 100%. CURRENTLY ENDEMIC IN EXTENSIVE REGIONS OF EURASIA, ASF IS OUT OF AFRICA FOREVER, A SITUATION THAT POSES A GRAVE THREAT TO THE US SWINE INDUSTRY. WHILE OUR CURRENT CONCERN IS ASFV GEORGIA-07, OTHER EMERGING ASFV STRAINS FROM AFRICAN RESERVOIRS THREATEN SWINE POPULATIONS FOR THE INDEFINITE FUTURE. ECONOMIC ANALYSIS INDICATES AN ASF OUTBREAK IN THE U.S. WOULD RESULT IN APPROXIMATELY $15 BILLION USD IN LOSSES, ASSUMING THE DISEASE IS RAPIDLY CONTROLLED.THERE IS NO VACCINE FOR ASF AVAILABLE. ALTHOUGH LIVE ATTENUATED VACCINES CURRENTLY UNDER DEVELOPMENT MIGHT BE HELPFUL IN ENDEMIC REGIONS,IT IS HARD TO IMAGINE A SCENARIO WHERE THEY WOULD BE SUITABLE FOR USE IN COUNTRIES WITH HIGHLY DEVELOPED SWINE INDUSTRIES LIKE THE U.S.; ISSUES OF EFFICACY, RESIDUAL PATHOGENICITY WITH IMMUNOPATHOLOGIC SEQUELAE, AND POTENTIAL FOR LONG-TERM VIRAL PERSISTENCE RAISE SIGNIFICANT SAFETYCONCERNS). EFFICACIOUS SUBUNIT/VECTORED ASF VACCINES WITH SIGNIFICANTLY ENHANCED SAFETY PROFILES ARE NEEDED FOR USE IN THE US.HERE, WE WILL: 1) EVALUATE PROTECTIVE EFFICACY OF ORF VIRUS AND PSEUDORABIES VIRUS VECTORS-EXPRESSING ASFV PROTECTICE ANTIGENS (PA) OF EPIDEMIC STRAIN GEORGIA-07 USING VACCINATION CHALLENGE EXPERIMENTS IN PIGS AND 2) IDENTIFY PA EPITOPES AND HOST RESPONSES ASSOCIATED WITH PROTECTION. PROJECT SUCCESS WILL PROVIDE CRITICAL FOUNDATIONAL INFORMATION NECESSARY FOR DESIGN/DEVELOPMENT OF SAFE AND EFFICACIOUS DIFFERENTIATE INFECTED FROM VACCINATED ANIMAL(DIVA) COMPATIBLE SUBUNIT OR VECTORED ASF VACCINES THAT WOULD BE OF CONSIDERABLE VALUE FOR EMERGENCY USE IN THE US SHOULD ASF BE INTRODUCED.